Omar, F. et al. (2019) Small-molecule allosteric activators of PDE4 long form cyclic AMP phosphodiesterases. Proceedings of the National Academy of Sciences of the United States of America, 116(27), pp. 13320-13329 VSports. (doi: 10. 1073/pnas. 1822113116) (PMID:31209056) (PMCID:PMC6613170) .
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Abstract
Cyclic AMP (cAMP) is a universal second messenger found in cells of all biological systems. In mammalian cells, it controls critical actions as diverse as cardiac function, cell proliferation, learning, and memory, for example VSports app下载. Even within a cell, it can differentially control distinct processes by virtue of compartmentalization, where targeted degradation by cAMP phosphodiesterases (PDEs) forms and shapes gradients that underpin this spatiotemporal organization. Here, we describe a small-molecule allosteric activator of PDE4 long isoforms. This discovery is poised to have considerable impact for both developing therapeutics and as a probe for gaining insight into the impact of PDE4 long isoforms upon the fundamental cellular processes that cAMP controls in health and disease.
| Item Type: | Articles |
|---|---|
| Additional Information: | A.C.M.O. and M.L. acknowledge research support from Kidney Research United Kingdom (Grant RP40/2014). E.K. acknowledges research support from Bundesministerium für Bildung und Forschung (16GW0179K), Deutsche Forschungsgemeinschaft (KL1415/7-1 and 394046635–SFB 1365), and the German–Israeli Foundation (I-1452- 203/13-2018). |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Baillie, Professor George and Omar, Miss Faisa and Fertig, Bracy |
| Authors: | Omar, F., Findlay, J. E., Carfray, G., Allcock, R. W., Jiang, Z., Moore, C., Muir, A. L., Lannoy, M., Fertig, B. A., Maie, D., Day, J. P., Bolger, G., Baillie, G. S., Schwiebert, E., Klussmann, E., Pyne, N. J., Ong, A. C.M., Bowers, K., Adam, J. M., Adams, D. R., Houslay, M. D., and Hendersona, D. J.P. |
| College/School: | College of Medical Veterinary and Life Sciences College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health |
| Journal Name: | Proceedings of the National Academy of Sciences of the United States of America |
| Publisher: | National Academy of Sciences |
| ISSN: | 0027-8424 |
| ISSN (Online): | 1091-6490 |
| Published Online: | 17 June 2019 |
| Copyright Holders: | Copyright © 2019 The Authors |
| First Published: | First published in Proceedings of the National Academy of Sciences of the United States of America 116(27): 13320-13329 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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